Suppressive effect of topoisomerase inhibitors on JC polyomavirus propagation in human neuroblastoma cells
| Autor: | Shigeki Sugiura, Takafumi Tasaki, Chiyoko Nukuzuma, Masanori Kameoka, Tsutomu Takegami, Kazuo Nakamichi, Souichi Nukuzuma |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
education.field_of_study medicine.drug_class viruses Progressive multifocal leukoencephalopathy Immunology Population Transfection Biology Topoisomerase-I Inhibitor medicine.disease Microbiology Virology 03 medical and health sciences 030104 developmental biology Plasmid Viral replication medicine Topotecan education Topoisomerase inhibitor medicine.drug |
| Zdroj: | Microbiology and Immunology. 60:253-260 |
| ISSN: | 0385-5600 |
| Popis: | JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease of the central nervous system, in immunocompromised patients. Because no drugs have been approved for treating PML, many antiviral agents are currently being investigated for this purpose. The inhibitory effects of the topoisomerase I inhibitors topotecan and β-lapachone were assessed by investigating viral replication, propagation and viral protein 1 (VP1) production in cultured cells. JCPyV replication was assayed using the human neuroblastoma cell line IMR-32 transfected with the JCPyV plasmid and RT- PCR combined with Dpn I treatment. Dpn I digests the input plasmid DNA containing methylated adenosine, but not newly replicated JCPyV DNA, in IMR-32 cells. It was found that JCPyV replicates less in IMR-32 cells treated with topotecan or β-lapachone than in untreated cells. Moreover, drug treatment of JCI cells, which are IMR-32 cells persistently infected with JCPyV, led to a reduction in the amount of JCPyV DNA and population of VP1-positive cells. These results demonstrate that topotecan and β-lapachone affects JCPyV propagation in human neuroblastoma cell lines, suggesting that topotecan and β-lapachone could potentially be used to treat PML. |
| Databáze: | OpenAIRE |
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